The beneficial effect of preoperative blood transfusions (random or donor-specific) on the survival of renal transplants (cadaver or living related) has been well documented. The mechanism(s) however are unknown despite extensive research. We will use the well defined donor-specific blood transfusion model in selected living related combinations in an attempt to identify mechanisms which contribute to the spectacular success of this model. We hope that the information obtained can be extended to the situation in which random blood transfusions are given. It is planned to investigate in detail 6 potential mechanisms in the donor-specific transfusion system. 1) Selection into high and low responders, 2) induction of unresponsiveness, 3) activation of specific and non-specific suppressor cells, 4) induction of antibodies, 5) immunomodulation of the recipient, and 6) in situ allograft changes. In vitro test systems such as MLC, CML, PLT, immunofluorescence, HLA serology, and monitoring of lymp]hocyte subsets with monoclonal antibodies will be used. In addition, the in situ allograft reaction will be investigated using fine needle aspiration cytology utilizing recently developed techniques of labelling cytocentrifuge preparations with monoclonal and anti-HLA-A, B, C, DR and Beta-2 antisera. The information gained from these experiments will be utilized to optimize the donor-specific blood transfusion protocol in an attempt to decrease sensitization, determine the effectiveness of immunosuppression during the administration of blood transfusions, and additionally come to conclusions about the mechanisms of random donor transfusions.